Peru-JHU TMRC Program Principal Investigator/Program Director (Last, First, Middle): GARCIA, Hector H. COMPONENT PROJECT 1 - IMPROVED DIAGNOSTICS ASSAYS FOR VIABLE OR DEGENERATING NEUROCYSTICERCOSIS Summary Taenia solium cysticercosis is the main cause of acquired epilepsy in developing countries and among the most common causes of this neurologic disease worldwide. The number, size, location, viability of CNS parasites, and the degrees of inflammation lead to highly pleomorphic clinical presentations, making neuroimaging examination (computed tomography [CT] or magnetic resonance imaging [MRI]) the diagnostic tool of choice. CT and MRI, however, are expensive and not accessible in poor rural areas, where neurocysticercosis (NCC) is highly endemic. Serologic tests play an important role in confirming the diagnosis in patients in whom imaging studies are not diagnostic. However, current serologic assays are clearly sub-optimal in three settingsCurrent serologic assays for the diagnosis of NCC are clearly sub-optimal in two settings: a) current tests are not sensitive in patients with a single brain lesion, due to poor sensitivity, and b) in extraparenchymal NCC, a type of NCC with a progressive course and bad prognosis, because the background prevalence of antibody in endemic regions results in a poor predictive value to discriminate these cases at higher risk of disease progression and severe morbidity. We have defined two diagnostic scenarios for which a confirmatory laboratory test is urgently required, Patients with a single viable or degenerating brain cyst, and Detecting extraparenchymal NCC. Single brain lesions have long differential diagnosis list. Since the prognosis and management of these conditions vary enormously a confirmatory test with higher sensitivity and specificity is needed. In the US, patients with single cysticercal lesions frequently undergo brain biopsy due to diagnostic uncertainty. Conversely, single lesions falsely thought to be single cysticercal cysts are sometimes unnecessarily left untreated in the watch and wait approach. The second target, a test which could accurately predict the presence of extraparenchymal NCC would permit identification of individuals with more severe disease for more complete studies resulting in earlier treatment and reduced morbidity and mortality. In many regions of the world there is no readily available brain imaging. Alternative assays or improvement of existing assays are urgently needed to overcome these drawbacks. Our preliminary findings using new antigens, and new assay technology suggest that we are poised to significantly improve the diagnosis by testing a series of novel techniques and platforms.Our overarching aim is to develop improved immunodiagnostic tests to solve defined clinical needs in human neurocysticercosis. And our specific aims are a) To develop a sensitive and specific test to confirm whether single brain lesions are due to cysticercosis and b) To develop and optimize a serodiagnostic assay to identify individuals who harbor extraparenchymal neurocysticercosis. This project will take advantage of a long established collaboration between the USA and Peru. The problem cannot be addressed easily in the United States because of the lack of the necessary infectious agent. Ultimately, if assays are efficacious, they will be applied in a medical setting to patients in the USA who are mainly from Latin American or other foreign countries.